2VXJ

CRYSTAL STRUCTURE OF PA-IL LECTIN COMPLEXED WITH AGAL13BGAL14GLC AT 1.9 A RESOLUTION

2VXJ の概要

• エントリーDOI: 10.2210/pdb2vxj/pdb
• 関連するPDBエントリー: 1L7L 1OKO 1UOJ
• 分子名称: PA-I GALACTOPHILIC LECTIN, alpha-D-galactopyranose-(1-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, alpha-D-galactopyranose-(1-3)-beta-D-galactopyranose-(1-4)-alpha-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: lectin, globoside, sugar binding protein
• 由来する生物種: PSEUDOMONAS AERUGINOSA
• 細胞内の位置: Cytoplasm: Q05097
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 320811.05

構造登録者

Blanchard, B.,Nurisso, A.,Hollville, E.,Tetaud, C.,Wiels, J.,Pokorna, M.,Wimmerova, M.,Varrot, A.,Imberty, A. (登録日: 2008-07-04, 公開日: 2008-09-16, 最終更新日: 2023-12-13)

主引用文献

Blanchard, B.,Nurisso, A.,Hollville, E.,Tetaud, C.,Wiels, J.,Pokorna, M.,Wimmerova, M.,Varrot, A.,Imberty, A.
Structural Basis of the Preferential Binding for Globo-Series Glycosphingolipids Displayed by Pseudomonas Aeruginosa Lectin I.
J.Mol.Biol., 383:837-, 2008

PubMed Abstract: The opportunistic pathogen Pseudomonas aeruginosa contains several carbohydrate-binding proteins, among which is the P. aeruginosa lectin I (PA-IL), which displays affinity for alpha-galactosylated glycans. Glycan arrays were screened and demonstrated stronger binding of PA-IL toward alphaGal1-4betaGal-terminating structures and weaker binding to alphaGal1-3betaGal ones in order to determine which human glycoconjugates could play a role in the carbohydrate-mediated adhesion of the bacteria. This was confirmed in vivo by testing the binding of the lectin to Burkitt lymphoma cells that present large amounts of globotriaosylceramide antigen Gb3/CD77/P(k). Trisaccharide moieties of Gb3 (alphaGal1-4betaGal1-4Glc) and isoglobotriaosylceramide (alphaGal1-3betaGal1-4Glc) were tested by titration microcalorimetry, and both displayed similar affinity to PA-IL in solution. The crystal structure of PA-IL complexed to alphaGal1-3betaGal1-4Glc trisaccharide has been solved at 1.9-A resolution and revealed how the second galactose residue makes specific contacts with the protein surface. Molecular modeling studies were performed in order to compare the binding mode of PA-IL toward alphaGal1-3Gal with that toward alphaGal1-4Gal. Docking studies demonstrated that alphaGal1-4Gal creates another network of contacts for achieving a very similar affinity, and 10-ns molecular dynamics in explicit water allowed for analyzing the flexibility of each disaccharide ligand in the protein binding site. The higher affinity observed for binding to Gb3 epitope, both in vivo and on glycan array, is likely related to the presentation effect of the oligosaccharide on a surface, since only the Gb3 glycosphingolipid geometry is fully compatible with parallel insertion of neighboring trisaccharide heads in two binding sites of the same tetramer of PA-IL.

PubMed: 18762193
DOI: 10.1016/J.JMB.2008.08.028

実験手法

X-RAY DIFFRACTION (1.9 Å)